Reduced dynamic range of antiviral innate immune responses in aging

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The worldwide population aged ≥ 65 years is increasing and the average life span is expected to increase another 10 years by 2050. This extended lifespan is associated with a progressive decline in immune function and a paradoxical state of low-grade, chronic inflammation that may contribute to susceptibility to viral infection, and reduced responses to vaccination. Here we review the effects of aging on innate immune responses to viral pathogens including elements of recognition, signaling, and production of inflammatory mediators. We specifically focus on age-related changes in key pattern recognition receptor signaling pathways, converging on altered cytokine responses, including a notable impairment of antiviral interferon responses. We highlight an emergent change in innate immunity that arises during aging – the dampening of the dynamic range of responses to multiple sources of stimulation – which may underlie reduced efficiency of immune responses in aging.HIGHLIGHTSWe review the effects of aging on innate antiviral immunity, including recognition, signaling, and cytokine responses.Lower Toll-like receptor expression leads to impaired signaling and responses upon activation of these sensors.Effects of aging on cytosolic nucleic acid sensing receptors and inflammasomes remains incompletely characterized.In aging the dynamic range of innate immunity is compressed, with increased basal activation of many signaling pathways.Interferon production is impaired with age, which may lead to the increased viral susceptibility of older persons.

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